Phase I Trial of the Multi-kinase Inhibitor Cabozantinib, a CYP3A4 Substrate, plus CYP3A4-Interacting Antiretroviral Therapy in People Living with HIV and Cancer (AMC-087).

Purpose: To evaluate the safety, pharmacokinetics, and pharmacodynamic effects of cabozantinib, a CYP3A4 substrate, in people living with human immunodeficiency virus and cancer receiving antiretrovirals (ARV).

Patients And Methods: Patients received a reduced dose of cabozantinib (20 mg orally daily) with strong CYP3A4 inhibitors (ARV ritonavir or non-ARV cobicistat, stratum A), or a standard 60 mg dose with ARVs that are CYP3A4 inducers (efavirenz or etravirine, stratum B) or noninteracting ARVs (stratum C). Initial dose escalation in stratum A and stratum B was performed on the basis of tolerability.

AMC-070: Lenalidomide Is Safe and Effective in HIV-Associated Kaposi Sarcoma.

Purpose: Kaposi sarcoma (KS), an endothelial cell tumor associated with KS herpesvirus (KSHV), remains among the most common malignancies occurring with HIV infection (HIV-KS). As an oral anti-inflammatory, antiangiogenic, and immunomodulatory agent, lenalidomide is potentially an attractive alternative to standard chemotherapy for KS.

Experimental Design: The primary objectives of this phase I/II trial were to determine the maximum tolerated dose (MTD) and response rates for lenalidomide in HIV-KS.

Pilot Trial AMC-063: Safety and Efficacy of Bortezomib in AIDS-associated Kaposi Sarcoma.

Purpose: AIDS-related Kaposi sarcoma is often incompletely controlled, requiring serial therapies. Kaposi sarcoma herpesvirus (KSHV) induces transformation of endothelial cells, where it resides in a predominately latent state. We hypothesized proteasome inhibition would have direct antitumor activity, induce lytic activation of KSHV, and inhibit HIV infectivity, improving control of both Kaposi sarcoma and HIV.

Safety and efficacy of an oncolytic viral strategy using bortezomib with ICE/R in relapsed/refractory HIV-positive lymphomas.

HIV-associated lymphomas (HALs) have high rates of latent infection by gammaherpesviruses (GHVs). We hypothesized that proteasome inhibition would induce lytic activation of GHVs and inhibit HIV infectivity via preservation of cytidine deaminase APOBEC3G, improving lymphoma control. We tested this oncolytic and antiviral strategy by using bortezomib combined with ifosfamide, carboplatin, and etoposide (ICE) alone or with rituximab (ICE/R) in relapsed/refractory HAL.

Utility of Bone Marrow Biopsy and Aspirate for Staging of Diffuse Large B Cell Lymphoma in the Era of Positron Emission Tomography With 2-Deoxy-2-[Fluorine-18]fluoro-deoxyglucose Integrated With Computed Tomography.

Background: About one-third of patients with diffuse large B cell lymphoma (DLBCL) have lymphomatous bone marrow involvement (BMI) at the time of diagnosis, and bone marrow aspirate/biopsy (BMAB) is considered the gold standard to detect such involvement. [F] fluorodeoxyglucose positron emission tomography combined with computed tomography (PET-CT), has become standard pretreatment imaging in DLBCL and may be a noninvasive alternative to BMAB to ascertain BMI. Prior studies have suggested that PET-CT scan may obviate the need for BMAB as a component for staging patients with newly diagnosed DLBCL, but this is not yet a standard of practice.

Long-term safety and efficacy of romiplostim for treatment of immune thrombocytopenia.

Inhibition of platelet production and mediated by antiplatelet antibodies is a well-known mechanism causing low platelet counts in immune thrombocytopenia (ITP). Use of thrombopoietin receptor agonists increases platelet counts and decreases the risk of bleeding in patients with ITP. Two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are approved by the US Food and Drug Administration to treat thrombocytopenia in adults, and most recently, children with persistent or chronic ITP.

Immune reconstitution inflammatory syndrome-associated Burkitt lymphoma after combination antiretroviral therapy in HIV-infected patients.

HIV/AIDS-associated immune reconstitution inflammatory syndrome (IRIS) is defined as a paradoxical worsening or unmasking of infections and autoimmune diseases, following initiation of combination anti-retroviral therapy (cART). More recently, the case definition of IRIS has been broadened to include certain malignancies including Kaposi’s sarcoma, and less frequently Hodgkin’s and non-Hodgkin’s lymphoma (NHL). Here in we describe 3 patients infected with HIV who began cART and within a median of 15 weeks each achieved non-detectable HIV viral loads, and yet within 6 months presented for medical attention with fevers, night sweats, weight loss and bulky lymphadenopathy.

Isolated granulocytic sarcoma of the nasopharynx: a case report and review of the literature.

Granulocytic sarcoma (GS) is a rare extramedullary manifestation of acute myeloid leukemia (AML). It may also represent blastic transformation of myelodysplastic syndromes or myeloproliferative neoplasms. Although usually seen in the context of advanced and poorly controlled disease, it may also present as the first manifestation of illness, without concurrent bone marrow or blood involvement.